http://www.medscape.com/viewarticle/725699

...To discern the etiology of PN in IPD patients, the authors examined a number of known causes of neuropathy, most of which were unrevealing. Although similar cobalamin levels were found in the IPD groups with and without PN, fasting homocysteine and methylmalonic acid (MMA) levels were significantly higher in the IPD group with PN.

The odds ratio for exposure to L-dopa in the IPD patients with PN was 12.4 (95% confidence interval, 1.4–109.1). ...Cumulative L-dopa exposure was associated not only with PN, but also with elevated fasting MMA levels across all IPD patients in the study. L-dopa exposure was also associated with PN severity in the IPD patients with PN.

This intriguing study demonstrates a somewhat unexpectedly high prevalence of PN in IPD patients and cites an association with elevated MMA levels, perhaps mediated by exposure to L-dopa. L-dopa may indeed interact with methylation pathways involved in folate metabolism, providing a mechanism for MMA elevation....if verified, this study may change the way we care for patients with IPD. PN in IPD could substantially contribute to gait disturbance and disability in some patients with IPD, and prevention of PN would be an important advance. Exposure to L-dopa is inevitable in most IPD patients at some point during their course, but perhaps we should be measuring MMA levels in these patients and treating with cobalamin supplementation to reduce MMA levels and prevent neuropathy. Further studies, including treatment trials, seem warranted.

(FYI: Methylmalonic acid is a precursor to the production of succinyl-CoA which is a key part of the Kreb’s cycle. Anyone who has studied biochemistry cringes when they hear the words “Kreb’s Cycle” because memorization and understanding of this process is the key to understanding human metabolism and energy production. The step of enzymatic conversion of the Methylmalonic –CoA into succinyl-CoA requires vitamin B12, and as a result methylmalonic acid levels are reliably elevated in patients with vitamin B12 deficiency.http://methylmalonicacid.org/)

I appreciate the fact that there are so many well-educated people who keep this forum informed. However, so many times I wish the information could be written so those of us who don't have your knowledge could understand what is being said, since it is so important to us also. (Just a thought)

there are a number of studies noting use of supplements Vitamin B 12 and folic acid in instances of B 12 deficiencies to decrease homocysteine levels that result. Levodopa reportedly interferes with folate metabolism and B 12 function.

Parkinsonism Relat Disord. 2008;14(4):321-5. Epub 2007 Dec 4.
Folate and vitamin B12 levels in levodopa-treated Parkinson's disease patients: their relationship to clinical manifestations, mood and cognition.

Abstract
We tested the hypothesis that mood, clinical manifestations and cognitive impairment of levodopa-treated Parkinson's disease (PD) patients are associated with vitamin B12 and folate deficiency...Levodopa-treated PD patients showed significantly lower serum levels of folate and vitamin B12 than neurological controls, while depressed patients had significantly lower serum folate levels as compared to non-depressed. Cognitively impaired PD patients exhibited significantly lower serum vitamin B12 levels as compared to cognitively non-impaired. In conclusion, lower folate levels were associated with depression, while lower vitamin B12 levels were associated with cognitive impairment. The effects of vitamin supplementation merit further attention and investigation.
PMID: 18055246 [PubMed - indexed for MEDLINE]


The influence of levodopa and the COMT inhibitor on serum vitamin B12 and folate levels in Parkinson's disease patients.
...Our findings show that levodopa-treated Parkinson's disease patients have low folate (p < 0.0007) and vitamin B12 levels (p < 0.0003). They also demonstrate that the addition of a COMT-i to levodopa + DDC-i treatment causes lower serum vitamin B12 (p < 0.03) and folate levels (p < 0.005) than levodopa + DDC-i treatment alone. We suggest supplementary treatment with vitamin B12 and folic acid in these situations.
http://www.ncbi.nlm.nih.gov/pubmed/17565222

Neurol Neurosurg Psychiatry 2003;74:549 doi:10.1136/jnnp.74.4.549
Correspondence
Benefit of folic acid supplementation in parkinsonian patients treated with levodopa
T Müller, D Woitalla, W Kuhn
+ Author Affiliations

Department of Neurology, St Josef Hospital, Ruhr University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany
Correspondence to:
 Dr T Müller; 
 thomas.mueller@ruhr-uni-bochum.de
We read with interest the recent excellent review by Reynolds on the role of folic acid and the risks and benefits of its supplementation in the nervous system.1 It emphasises the beneficial importance of folate on the numerous methylation processes in combination with S-adenosylmethionine (SAM), which donates its methyl group to prevent hyperhomocysteinaemia.1 However SAM deficiency, which is associated with, for example, cognitive decline and/or mood disturbances, and increased total homocysteine levels, which support onset of vascular disease, may also caused by drugs, for example, levodopa.2,3 Levodopa is administered with dopa decarboxylase inhibitors (DDI) to prevent its peripheral degradation. This increases conversion of levodopa to 3-O-methyldopa (3-OMD) by the ubiquitious enzyme catechol-O-methyltransferase (COMT) in blood, peripheral tissues and in nigrostriatal neurons.2,3 COMT requires Mg2+ as cofactor and SAM as methyl donor. Thus O-methylation of levodopa to 3-OMD is associated with conversion of SAM to S-adenosylhomocysteine and subsequently homocysteine.

http://jnnp.bmj.com/content/74/4/549.1.full

(B12 supplement should be "under the tongue" or sublingual form. stomach acids render an oral form useless.
For those individuals who have had DNA profiling, check for polymorphisms of the methylenetetrahydrofolate reductase (MTHFR C677T), methyltetrahydrofolate-homocysteine methyltransferase (MTR A2756G), and 5-methyltetrahydrofolate-homocysteine methyltransferase reductase both associated with folate metabolism and in addition, check (MTRR A1049G and C1783T) associated with processing of B12 in the bodY. If you have mutations in the MTHFR gene, must use a breakdown product of folic acid, methyl folate, and folinic acid if one has the other mutation. Mutations in MTRR requires a B 12 supplement.

Sorry--in my haste (I find I have so little time for anything other than caretaking these days) I did not consider what message I thought important from the article--which is: Levodopa depletes B12 and interferes with folate metabolism and thus folic acid, necessitating supplementation with B 12 and Folic acid. SNPs (mutations) in the gene coding folic acid are very common. Individuals who have these SNPs need to use the breakdown product of folic acid--5-MTHF and folinic acid (I know Thorne makes a prodcut with this combo as does Metagenics; I do not know of others.)
madelyn